SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer
| Autor: | Qiqi Shi, Neelum Aziz Yousafzai, Vivian Y. Shin, Lifeng Feng, Hongchuan Jin, Jinye Xu, Wenxia Xu, Qiyin Zhou, Xian Wang, Hui Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research DNA Repair Apoptosis Mice XRCC1 0302 clinical medicine Sirtuin 1 Ubiquitin Cancer Gene knockdown biology Chemistry lcsh:Cytology DNA Neoplasm Ubiquitin ligase Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Lung cancer Signal Transduction DNA damage Immunology Carbazoles Antineoplastic Agents Respiratory Mucosa Article 03 medical and health sciences Cellular and Molecular Neuroscience Cell Line Tumor medicine Animals Humans Amino Acid Sequence lcsh:QH573-671 Sequence Homology Amino Acid Ubiquitination Cell Biology beta-Transducin Repeat-Containing Proteins medicine.disease X-ray Repair Cross Complementing Protein 1 030104 developmental biology Drug Resistance Neoplasm biology.protein Cancer research Protein deacetylase Cisplatin Protein Processing Post-Translational Sequence Alignment DNA Damage |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 5, Pp 1-12 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1592-3 |
| Popis: | Chemoresistance is one of the most important challenges in the clinical management of lung cancer. SIRT1 is a NAD dependent protein deacetylase and implicated in diverse cellular processes such as DNA damage repair, and cancer progression. SIRT1 is upregulated in chemoresistant lung cancer cells, genetic knockdown or chemical inhibition of SIRT1 reversed chemoresistance by enhancing DNA damage and apoptosis activation, accompanied with XRCC1 degradation. E3 ligase β-TrCP catalyzed the poly-ubiquitination of XRCC1 to promote its proteasome-dependent degradation. SIRT1 bound and deacetylated XRCC1 at lysine K260, K298 and K431, preventing it from β-TrCP-dependent ubiquitination. Mutations of these three lysine sites in XRCC1 abrogated the interaction with β-TrCP and prolonged the half-life of XRCC1 protein. Here, we describes SIRT1 confers chemoresistance to lung cancer cells by deacetylating and stabilizing XRCC1. Therefore, targeting SIRT1 might be a new strategy to manage the chemoresistance of lung cancer, and probably other cancers. |
| Databáze: | OpenAIRE |
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